A method is being developed for the estimation of local rates of protein synthesis in brain in vivo. The method is based on the use of L-(1-14C)leucine as a tracer for the incorporation of leucine into protein. A model of the behavior of leucine and (l-14C)leucine has been designed. By mathematical analysis of the kinetics of exchange of the amino acid between plasma and tissue and its incorporation into protein, an equation has been derived that defines the rate of amino acid incorporation into protein in terms of the time course of plasma specific activity, final tissue concentration of 14C, and experimentally determined kinetic constants. Tissue concentrations of 14C are determined by quantitative autoradiography. The method is currently being applied to studies of development, cretinism, plasticity in the visual system, seizures, regeneration, and sleep.